Molecular genetics of the Rh blood group system: alleles and antibodies—a narrative review

Objective: This work proposes a review of the antibodies which have been associated with variant RHD and RHCE alleles, except null alleles. Background: The data on this topic is dispersed in the literature. Methods: A review of the articles referenced in PubMed and of abstract books from major conferences was performed. Most antibodies have been published in full-length articles, and several more have been reported in conference abstracts. The anti-D antibodies reported in carriers of D variants and the antibodies to CE antigens reported in carriers of CE variants were listed, including antibodies to low prevalence antigens. The RHCE alleles for which the RH10 (V) and RH20 (VS) phenotypes have been reported were also collected. The reports of antibody formation were compared to the prevalence evaluated by the Erythrogene database in the 1000 Genomes dataset. Conclusions: It is noted in this review that studies reporting anti-D or antibodies to CE antigens associated with Rh variants only rarely include detailed serological descriptions of the findings. This review lists several alleles which are not exceptional, and for which no carrier has been reported to form the antibody to the expressed antigen(s) (e.g., no allo-anti-D has been reported so far in carriers of RHD*01EL.01, c.1227A). Considering the antibody reports in carriers or absence thereof and the prevalence for each RH allele, it may become possible to propose case-by-case recommendations for more RH alleles in the near future.